Incidental Mutation 'R9617:Map3k4'
ID 726544
Institutional Source Beutler Lab
Gene Symbol Map3k4
Ensembl Gene ENSMUSG00000014426
Gene Name mitogen-activated protein kinase kinase kinase 4
Synonyms T-associated sex reversal, D17Rp17, D17Rp17e, Mekk4, Tas, RP17, MAPKKK4, MTK1
MMRRC Submission
Accession Numbers
Essential gene? Probably essential (E-score: 0.958) question?
Stock # R9617 (G1)
Quality Score 225.009
Status Not validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 12476871 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 759 (S759P)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect possibly damaging
Transcript: ENSMUST00000089058
AA Change: S759P

PolyPhen 2 Score 0.669 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: S759P

DomainStartEndE-ValueType
low complexity region 8 21 N/A INTRINSIC
low complexity region 27 43 N/A INTRINSIC
low complexity region 215 235 N/A INTRINSIC
low complexity region 432 462 N/A INTRINSIC
low complexity region 1177 1191 N/A INTRINSIC
S_TKc 1332 1590 1.41e-91 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous null mice exhibit some perinatal lethality and survivors appear smaller. On certain genetic backgrounds, heterozygous X/Y mice may develop as phenotypic females or hermaphrodites. The sex-reversal phenotype is dependent on a combination of strain-specific autosomal and Y-linked alleles. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110032F04Rik C T 3: 68,777,402 (GRCm39) P121L probably damaging Het
4930442H23Rik C T 10: 81,018,976 (GRCm39) V16I unknown Het
4930444P10Rik T C 1: 16,139,051 (GRCm39) M97V probably benign Het
Abcb1a A T 5: 8,797,353 (GRCm39) probably null Het
Abhd5 T C 9: 122,197,035 (GRCm39) I74T probably benign Het
Ankle2 T A 5: 110,399,409 (GRCm39) F590I probably damaging Het
C2cd6 T C 1: 59,097,848 (GRCm39) S414G probably benign Het
Catsperd G A 17: 56,968,252 (GRCm39) D546N probably benign Het
Cep295nl G T 11: 118,224,000 (GRCm39) H281Q possibly damaging Het
Cfap69 T C 5: 5,639,164 (GRCm39) E670G probably damaging Het
Cfh A T 1: 140,090,718 (GRCm39) V90E possibly damaging Het
Cnksr3 A C 10: 7,079,021 (GRCm39) probably null Het
Cntrl T A 2: 35,035,077 (GRCm39) F901L probably benign Het
Coch T A 12: 51,645,034 (GRCm39) M196K probably damaging Het
Crygd T C 1: 65,102,369 (GRCm39) N34S probably damaging Het
Ctdp1 A T 18: 80,492,962 (GRCm39) I511N probably benign Het
Dhx30 C T 9: 109,926,186 (GRCm39) A142T probably damaging Het
Dlg2 T C 7: 92,087,284 (GRCm39) probably null Het
Dmxl1 A G 18: 49,998,228 (GRCm39) D776G probably damaging Het
Dnm3 C T 1: 162,149,354 (GRCm39) G197D probably damaging Het
Eif4g3 A G 4: 137,824,190 (GRCm39) H91R probably damaging Het
Ephb6 A G 6: 41,596,258 (GRCm39) M844V probably damaging Het
Erc1 T C 6: 119,773,902 (GRCm39) E351G probably benign Het
Etfbkmt G A 6: 149,045,744 (GRCm39) G33R probably benign Het
Fnbp4 T C 2: 90,588,738 (GRCm39) I503T probably benign Het
Gm6370 A T 5: 146,429,993 (GRCm39) Q143L probably benign Het
Gnas T C 2: 174,141,988 (GRCm39) V719A possibly damaging Het
H13 C A 2: 152,530,873 (GRCm39) D219E probably damaging Het
Hhatl G A 9: 121,618,191 (GRCm39) T188I possibly damaging Het
Ifi27l2b C T 12: 103,422,683 (GRCm39) A45T probably damaging Het
Kbtbd8 T C 6: 95,103,874 (GRCm39) C585R possibly damaging Het
Limk2 A G 11: 3,297,715 (GRCm39) S473P probably damaging Het
Lrba G A 3: 86,267,169 (GRCm39) G1620S probably benign Het
Lrrtm2 T C 18: 35,346,490 (GRCm39) T271A probably benign Het
Mybphl G T 3: 108,282,952 (GRCm39) V247F possibly damaging Het
Myh10 T A 11: 68,682,815 (GRCm39) V1120D probably benign Het
Naip1 T C 13: 100,569,821 (GRCm39) N271S probably benign Het
Napepld C T 5: 21,875,561 (GRCm39) V328I probably damaging Het
Nucb1 A G 7: 45,148,159 (GRCm39) V218A probably benign Het
Nup107 A T 10: 117,593,238 (GRCm39) D813E probably benign Het
Or14j3 T A 17: 37,901,053 (GRCm39) K64* probably null Het
Or5g29 T A 2: 85,421,279 (GRCm39) Y132N probably damaging Het
Or6c35 A T 10: 129,168,794 (GRCm39) T15S probably damaging Het
Or8g52 A G 9: 39,630,678 (GRCm39) S52G possibly damaging Het
Pabpc2 T C 18: 39,907,602 (GRCm39) I289T probably benign Het
Parg A G 14: 31,960,569 (GRCm39) I600V probably benign Het
Patj T C 4: 98,393,991 (GRCm39) F975L probably benign Het
Pcdhb17 A G 18: 37,618,218 (GRCm39) T3A probably benign Het
Piezo2 T C 18: 63,248,108 (GRCm39) E464G probably benign Het
Pkd1 T A 17: 24,800,341 (GRCm39) V3034D probably damaging Het
Pld2 A G 11: 70,447,944 (GRCm39) E869G probably damaging Het
Plek T A 11: 16,945,311 (GRCm39) L29F possibly damaging Het
Prelp A G 1: 133,842,416 (GRCm39) L243P probably damaging Het
Rapgef5 T A 12: 117,621,930 (GRCm39) D231E probably benign Het
Riok1 A G 13: 38,244,016 (GRCm39) E514G probably benign Het
Rmdn2 T C 17: 79,928,790 (GRCm39) M14T probably benign Het
Rorb G A 19: 18,939,499 (GRCm39) Q228* probably null Het
Scmh1 T A 4: 120,340,827 (GRCm39) M171K probably damaging Het
Scn9a A G 2: 66,392,809 (GRCm39) L261P probably damaging Het
Senp7 A T 16: 55,971,652 (GRCm39) N263I probably benign Het
Slc11a1 G T 1: 74,419,041 (GRCm39) A162S probably benign Het
Slc6a17 A G 3: 107,384,685 (GRCm39) V305A probably damaging Het
Snph A T 2: 151,435,422 (GRCm39) V502E probably damaging Het
Sost G T 11: 101,854,892 (GRCm39) A139E possibly damaging Het
Srp54a A T 12: 55,136,061 (GRCm39) E25D probably benign Het
Tmeff1 T A 4: 48,636,940 (GRCm39) C213S probably damaging Het
Tmem232 A T 17: 65,807,180 (GRCm39) Y4* probably null Het
Tmem63c T G 12: 87,103,361 (GRCm39) I45S probably benign Het
Ttbk1 C T 17: 46,757,998 (GRCm39) G879S probably damaging Het
Ugt1a7c A G 1: 88,022,952 (GRCm39) H37R probably damaging Het
Vmn1r236 T C 17: 21,507,053 (GRCm39) L57P probably damaging Het
Wnk2 T A 13: 49,192,453 (GRCm39) E675V unknown Het
Wnt10b T C 15: 98,674,609 (GRCm39) T43A probably damaging Het
Wnt8a C A 18: 34,680,163 (GRCm39) T176K probably benign Het
Zfp937 T A 2: 150,080,452 (GRCm39) C161S probably damaging Het
Other mutations in Map3k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01065:Map3k4 APN 17 12,451,877 (GRCm39) missense probably damaging 1.00
IGL01124:Map3k4 APN 17 12,474,087 (GRCm39) missense probably benign 0.01
IGL01125:Map3k4 APN 17 12,490,849 (GRCm39) missense probably damaging 0.96
IGL01585:Map3k4 APN 17 12,467,846 (GRCm39) missense probably damaging 1.00
IGL02194:Map3k4 APN 17 12,482,815 (GRCm39) missense probably damaging 1.00
IGL02194:Map3k4 APN 17 12,467,882 (GRCm39) missense probably benign 0.30
IGL02292:Map3k4 APN 17 12,454,045 (GRCm39) missense possibly damaging 0.77
IGL02326:Map3k4 APN 17 12,467,897 (GRCm39) missense probably damaging 1.00
IGL02388:Map3k4 APN 17 12,490,497 (GRCm39) missense probably damaging 0.99
IGL02621:Map3k4 APN 17 12,482,900 (GRCm39) missense probably damaging 1.00
IGL02668:Map3k4 APN 17 12,454,840 (GRCm39) missense possibly damaging 0.85
IGL02850:Map3k4 APN 17 12,490,801 (GRCm39) missense probably damaging 1.00
IGL02939:Map3k4 APN 17 12,491,036 (GRCm39) missense probably damaging 1.00
IGL03148:Map3k4 APN 17 12,457,045 (GRCm39) missense probably benign 0.01
IGL03238:Map3k4 APN 17 12,490,045 (GRCm39) missense probably benign 0.10
ANU74:Map3k4 UTSW 17 12,451,863 (GRCm39) missense probably damaging 1.00
R0012:Map3k4 UTSW 17 12,457,076 (GRCm39) missense probably damaging 1.00
R0012:Map3k4 UTSW 17 12,457,076 (GRCm39) missense probably damaging 1.00
R0128:Map3k4 UTSW 17 12,466,950 (GRCm39) missense probably damaging 0.99
R0183:Map3k4 UTSW 17 12,454,015 (GRCm39) missense probably damaging 1.00
R0309:Map3k4 UTSW 17 12,489,902 (GRCm39) frame shift probably null
R0355:Map3k4 UTSW 17 12,473,058 (GRCm39) missense probably damaging 1.00
R0367:Map3k4 UTSW 17 12,476,928 (GRCm39) splice site probably benign
R1103:Map3k4 UTSW 17 12,455,950 (GRCm39) splice site probably null
R1446:Map3k4 UTSW 17 12,475,681 (GRCm39) nonsense probably null
R1542:Map3k4 UTSW 17 12,454,793 (GRCm39) missense probably damaging 0.97
R1713:Map3k4 UTSW 17 12,468,458 (GRCm39) missense probably benign 0.39
R1777:Map3k4 UTSW 17 12,490,617 (GRCm39) missense possibly damaging 0.82
R1797:Map3k4 UTSW 17 12,482,906 (GRCm39) missense probably benign 0.30
R1997:Map3k4 UTSW 17 12,473,882 (GRCm39) critical splice donor site probably null
R2042:Map3k4 UTSW 17 12,496,870 (GRCm39) missense probably damaging 0.99
R2878:Map3k4 UTSW 17 12,482,954 (GRCm39) missense probably benign 0.00
R2939:Map3k4 UTSW 17 12,480,157 (GRCm39) missense probably damaging 0.98
R2940:Map3k4 UTSW 17 12,480,157 (GRCm39) missense probably damaging 0.98
R3405:Map3k4 UTSW 17 12,475,668 (GRCm39) missense probably damaging 1.00
R3930:Map3k4 UTSW 17 12,454,880 (GRCm39) missense possibly damaging 0.83
R4291:Map3k4 UTSW 17 12,474,147 (GRCm39) missense probably benign 0.08
R4410:Map3k4 UTSW 17 12,467,885 (GRCm39) missense probably damaging 1.00
R4632:Map3k4 UTSW 17 12,451,391 (GRCm39) missense probably damaging 1.00
R4641:Map3k4 UTSW 17 12,482,932 (GRCm39) missense probably damaging 1.00
R4726:Map3k4 UTSW 17 12,451,851 (GRCm39) missense possibly damaging 0.89
R4730:Map3k4 UTSW 17 12,467,861 (GRCm39) missense probably damaging 0.99
R4832:Map3k4 UTSW 17 12,490,667 (GRCm39) missense probably damaging 1.00
R4896:Map3k4 UTSW 17 12,490,906 (GRCm39) missense possibly damaging 0.65
R4934:Map3k4 UTSW 17 12,490,787 (GRCm39) missense probably damaging 1.00
R4971:Map3k4 UTSW 17 12,468,382 (GRCm39) critical splice donor site probably null
R4980:Map3k4 UTSW 17 12,490,958 (GRCm39) missense probably damaging 1.00
R5211:Map3k4 UTSW 17 12,451,321 (GRCm39) missense possibly damaging 0.88
R5337:Map3k4 UTSW 17 12,490,497 (GRCm39) missense probably damaging 0.99
R5356:Map3k4 UTSW 17 12,466,195 (GRCm39) missense possibly damaging 0.87
R5550:Map3k4 UTSW 17 12,462,445 (GRCm39) nonsense probably null
R5824:Map3k4 UTSW 17 12,448,526 (GRCm39) missense probably damaging 1.00
R5890:Map3k4 UTSW 17 12,490,303 (GRCm39) missense probably damaging 1.00
R6285:Map3k4 UTSW 17 12,482,945 (GRCm39) missense probably damaging 1.00
R6380:Map3k4 UTSW 17 12,490,954 (GRCm39) missense possibly damaging 0.56
R6383:Map3k4 UTSW 17 12,468,470 (GRCm39) missense possibly damaging 0.82
R6571:Map3k4 UTSW 17 12,461,579 (GRCm39) missense possibly damaging 0.80
R6584:Map3k4 UTSW 17 12,479,378 (GRCm39) missense probably damaging 1.00
R6616:Map3k4 UTSW 17 12,490,231 (GRCm39) missense probably damaging 1.00
R6644:Map3k4 UTSW 17 12,451,297 (GRCm39) critical splice donor site probably null
R6909:Map3k4 UTSW 17 12,489,872 (GRCm39) missense probably damaging 1.00
R6947:Map3k4 UTSW 17 12,479,456 (GRCm39) nonsense probably null
R6970:Map3k4 UTSW 17 12,467,803 (GRCm39) missense probably damaging 1.00
R7120:Map3k4 UTSW 17 12,490,354 (GRCm39) missense probably damaging 1.00
R7253:Map3k4 UTSW 17 12,490,955 (GRCm39) missense probably benign 0.00
R7267:Map3k4 UTSW 17 12,490,536 (GRCm39) nonsense probably null
R7322:Map3k4 UTSW 17 12,489,833 (GRCm39) missense probably damaging 1.00
R7522:Map3k4 UTSW 17 12,480,219 (GRCm39) missense probably benign 0.39
R7554:Map3k4 UTSW 17 12,451,300 (GRCm39) missense probably damaging 1.00
R7554:Map3k4 UTSW 17 12,451,301 (GRCm39) nonsense probably null
R7681:Map3k4 UTSW 17 12,537,430 (GRCm39) missense unknown
R7734:Map3k4 UTSW 17 12,482,998 (GRCm39) missense probably damaging 1.00
R7842:Map3k4 UTSW 17 12,490,030 (GRCm39) missense possibly damaging 0.54
R8013:Map3k4 UTSW 17 12,489,918 (GRCm39) nonsense probably null
R8014:Map3k4 UTSW 17 12,489,918 (GRCm39) nonsense probably null
R8235:Map3k4 UTSW 17 12,458,968 (GRCm39) splice site probably null
R8294:Map3k4 UTSW 17 12,537,500 (GRCm39) missense unknown
R8528:Map3k4 UTSW 17 12,451,821 (GRCm39) missense probably damaging 1.00
R8858:Map3k4 UTSW 17 12,490,759 (GRCm39) missense probably damaging 1.00
R8924:Map3k4 UTSW 17 12,490,433 (GRCm39) missense probably benign 0.00
R9063:Map3k4 UTSW 17 12,482,878 (GRCm39) missense probably damaging 1.00
R9224:Map3k4 UTSW 17 12,456,973 (GRCm39) missense probably damaging 0.99
R9446:Map3k4 UTSW 17 12,451,375 (GRCm39) missense probably damaging 1.00
R9486:Map3k4 UTSW 17 12,489,860 (GRCm39) missense probably damaging 1.00
R9488:Map3k4 UTSW 17 12,489,860 (GRCm39) missense probably damaging 1.00
R9591:Map3k4 UTSW 17 12,454,795 (GRCm39) missense possibly damaging 0.91
R9722:Map3k4 UTSW 17 12,490,523 (GRCm39) missense probably benign 0.01
X0067:Map3k4 UTSW 17 12,482,981 (GRCm39) missense probably benign 0.03
Z1177:Map3k4 UTSW 17 12,490,584 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CAGCCATGTTCAGCTAATATCCAC -3'
(R):5'- CACCAGGTTTATAGTCAGTGCTG -3'

Sequencing Primer
(F):5'- ATCATGTTAAAGTCTGTTTGCCTG -3'
(R):5'- TCAGTGCTGTGTATTAGAACAAAGG -3'
Posted On 2022-10-06